rs17832998

Positions:

• chr14-58646014-C-G
• chr14-58646014-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001079520.2(DACT1):​c.1280C>G​(p.Ala427Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A427V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DACT1 NM_001079520.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

Genes affected

DACT1 (HGNC:17748): (dishevelled binding antagonist of beta catenin 1) The protein encoded by this gene belongs to the dapper family, characterized by the presence of PDZ-binding motif at the C-terminus. It interacts with, and positively regulates dishevelled-mediated signaling pathways during development. Depletion of this mRNA from xenopus embryos resulted in loss of notochord and head structures, and mice lacking this gene died shortly after birth from severe posterior malformations. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

DACT1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06944206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACT1	NM_001079520.2	c.1280C>G	p.Ala427Gly	missense_variant	4/4	ENST00000395153.8	NP_001072988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACT1	ENST00000395153.8	c.1280C>G	p.Ala427Gly	missense_variant	4/4	5	NM_001079520.2	ENSP00000378582.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250366 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135506

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.3
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T;.;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.62	.;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	.;.;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.066	T;T;T;T
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.015	.;.;B;.
Vest4		0.089
MutPred		0.077		.;.;Gain of relative solvent accessibility (P = 0.0215);.;
MVP		0.37
MPC		0.19
ClinPred		0.037	T
GERP RS		2.4
Varity_R		0.079
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17832998; hg19: chr14-59112732;